The human sexual response in both males and females results from a complex interplay of psychological, hormonal, and other physiological influences. One important aspect of the human sexual response common to both men and women is the erectile response, which itself results from an interplay between the autonomic nervous system, the endocrine system, and the circulatory system.
Failure of the erectile response, while occurring in both sexes, is most common in men and is referred to as impotence or Erectile Dysfunction (ED). ED is defined as the persistent inability to attain and maintain an erection adequate to permit satisfactory performance. While generally considered a benign disorder, ED has a significant impact on the quality of life experienced by many individuals. It is estimated that 30 million Americans and an additional 46 million men in industrialized countries suffer from some form of ED. The incidence of ED increases with age from about 2 percent at age 40 to about 25% at age 65. In addition, ED is closely associated with certain medical conditions such as cardiovascular disease, hypertension, and diabetes, as well with use of certain prescription medications.
Until recently, medical solutions for ED were invasive, expensive, and often ineffective. These solutions most often included injectable drugs, implants, and pumps. They were met with less than enthusiastic support by patients and obvious drawbacks included pain, risk of infection, inconvenience, and interference with spontaneity. Within the past few years, Pfizer's orally active product Viagra® (sildenafil citrate) has become a break-though treatment for ED. Sildenafil is a potent and selective cGMP-specific type 5 phosphodiesterase inhibitor and now represents the first line therapy for the treatment of ED. Despite sildenafil's success, however, numerous patients have not been successfully treated. In addition, sildenafil must be administered significantly prior to sexual activity ruining spontaneity and numerous side effects have been reported. The most significant side effects relate to visual impairment.
An aspect of the present invention is directed towards novel a receptor antagonists for the treatment of inadequate erectile response. The compounds of the present invention (Formula I) will present another line of therapy for this serious condition in both men and women.